Researchers at Children’s Hospital Boston and other Harvard Medical School centers studied alterations in brain structure in male and female age-matched interictal (migraine free) migraineurs and controls, using high-field MRI. Female migraineurs had thicker posterior insula and precuneus cortices and functional differences in response to noxious stimuli compared with male migraineurs and healthy controls of both sexes. Female migraineurs show greater activation in brain regions involved in emotional processing: amygdala, parahippocampus, basal ganglia and posterior cingulate cortex. 
COMMENT. These findings may be important in therapy of migraine and development of specific drugs for female migraineurs, targeting stress related disorders. Papez’ circuit, a major pathway of the limbic system that controls emotion, is involved in female migraine. The initial description of the pathway by Papez is as follows: hippocampal formation, fornix, mammillary bodies, mammillothalamic tract, anterior thalamic nucleus, internal capsule, cingulate gyrus, parahippocampal gyrus, entorhinal cortex, hippocampus. The prefrontal cortex and amygdala were included later in a larger loop or “circuit of emotion.” 
Therapeutic strategies in migraine patients with mood and anxiety disorders list amitriptyline, flunarizine, pregabalin, valproate, topiramate, and lamotrigine (for migraine with aura).